Targeted Mesoporous Silica Nanoparticles Delivering Arsenic Trioxide with Environment Sensitive Drug Release for Effective Treatment of Triple Negative Breast Cancer

In this study, we report a novel modality of using a mesoporous silica nanoparticles (MSNs)-based drug delivery system with RGD peptide as a targeting ligand to load arsenic trioxide (ATO) (ATO-MSNs-RGD) for treating MDA-MB-231 triple -negative breast cancer. The MSNs, ATO-MSNs, and ATO-MSNs-RGD were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and BrunauerEmmet-Teller (BET) method. The data indicated that the MSNs possessed MCM-41 type mesopores with high surface area of similar to 1021 m(2)/g and pore diameter of similar to 2.2 nm. However, both values dramatically decreased after MSNs were encapsulated with ATO or modified with RGD. The amount of surface anchored RGD peptide was determined to be 0.20 mmol/g. Glutathione (GSH) greatly enhanced ATO release from MSNs. Confocal laser microscopy images demonstrated that both ATO-MSNs and ATOMSNs-RGD had good cellular uptake that improved with longer incubation time and nanoparticle concentration and the ATOMSNs-RGD showed clearly improved cellular uptake compared with ATO-MSNs. The MSNs, ATO-MSNs, ATO-MSNs-RGD, and ATO were used to treat mice bearing MDA-MB-231 breast tumors every 5 days and the findings suggested that ATOMSNs-RGD provided superior therapeutic ability over MSNs, ATO-MSNs, and ATO.